Transthyretin Amyloidosis Cardiomyopathy in Patients With HFpEF in Russia (TETRAMER)

Multicenter Observational Retrospective-prospective Study of Prevalence and Clinical Characteristics of Transthyretin Amyloidosis Cardiomyopathy in Russian Patients With Heart Failure With Preserved Ejection Fraction in Real Clinical Practice

A multicenter observational retrospective-prospective study of prevalence and clinical characteristics of transthyretin amyloidosis (ATTR) cardiomyopathy (CM) in Russian patients with heart failure with preserved ejection fraction (HFpEF) in real clinical practice.

The retrospective phase will entail secondary data collection from electronic or paper medical records of patients who are participating/participated in the PRIORITY-CHF study and have HFpEF. Those patients who have a high suspicion of having ATTR-CM and provided informed consent will be invited to participate in the prospective phase. The prospective phase will consist of three visits, during which a routine comprehensive cardiologic evaluation in order to confirm or exclude ATTR-CM diagnosis will be performed. In patients with confirmed ATTR-CM the material for genetic testing will be collected in order to specify the type of ATTR-amyloidosis

Study Overview

• Status: Terminated
• Conditions: Transthyretin Amyloidosis Cardiomyopathy, Heart Failure With Preserved Ejection Fraction

Detailed Description

This is a multicenter observational study consisting of retrospective and prospective phases.

Heart failure (HF) - is a clinical syndrome characterised by the presence of typical symptoms (e.g. breathlessness, fatigue and ankle swelling) and signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress.

Cardiac amyloidosis is an underestimated cause of HF and cardiac arrhythmias. Among all most commonly types of cardiac amyloidosis (wild-type or familial TTR and light-chain), the wild-type (Wt) TTR-related amyloidosis (ATTR) is an increasingly recognized cause of HFpEF, and amyloidosis should be considered in the differential diagnosis of this heart failure group of patients.

ATTR-CM is an inexorably progressive and eventually fatal, associated with poor quality of life. Diagnosis is often delayed for many years after symptoms develop. However, recognition of ATTR epidemiology is evolving due to the increased use of cardiac scintigraphy as a noninvasive diagnostic tool. Early identification and intervention are crucial to improve patient outcomes because newly available treatments have been shown to have maximum therapeutic benefit when started in the early stages of the disease. In recent years, contemporary cardiac imaging techniques, including MRI and bone scintigraphy, have altered the diagnostic algorithm for ATTR-CM, which has resulted in increased detection.

Thus country-specific epidemiologic data collection and identification of ATTR-CM is crucial to improve outcomes and quality of life. However, no observational studies on the epidemiology of ATTR-CM in Russian patients with HFpEF have been performed.

Therefore, there is a need to conduct a large-scale observational study to determine the prevalence of ATTR-CM in Russia, obtain information on patients' clinical characteristics, and determine their medical needs. Meanwhile information about epidemiological, ECG, EchoCG, other characteristics and prevalence is crucially important to improve diagnostics of these patients.

In addition, recently molecular genetic testing became available, which is essential to diagnose hereditary ATTR. Earlier recognition of the ATTR type, in turn, may lead to timely treatment initiation and change in the prognostic outlook of ATTR-CM patients.

• Study Type: Observational
• Enrollment (Actual): 1770

Contacts and Locations

Study Locations

• Russia
  • Akhtubinsk, Russia
    • Research Site
  • Astrakhan, Russia
    • Research Site
  • Barnaul, Russia
    • Research Site
  • Beslan, Russia
    • Research Site
  • Chelyabinsk, Russia
    • Research Site
  • Izhevsk, Russia
    • Research Site
  • Kaluga, Russia
    • Research Site
  • Kazan', Russia
    • Research Site
  • Khabarovsk, Russia
    • Research Site
  • Kirov, Russia
    • Research Site
  • Krasnodar, Russia
    • Research Site
  • Nizhny Novgorod, Russia
    • Research Site
  • Omsk, Russia
    • Research Site
  • Rostov-on-Don, Russia
    • Research Site
  • Smolensk, Russia
    • Research Site
  • Ufa, Russia
    • Research Site
  • Vladimir, Russia
    • Research Site
  • Vladivostok, Russia
    • Research Site
  • Volgograd, Russia
    • Research Site
  • Yaroslavl, Russia
    • Research Site
  • Yekaterinburg, Russia
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Planned study population consists of approximately 6000 patients with HFpEF who are participating/participated in the PRIORITY-CHF study and will be enrolled to this study across 140 clinical centers in different regions of Russia, in order to provide a representative study sample. Those patients who have a high suspicion of having ATTR-CM and provided informed consent will be invited to participate in the prospective phase. The patients will be included to the current study consecutively, from the earliest date of start of participation in the PRIORITY-CHF study.

Description

Inclusion Criteria:

for the retrospective phase are:

• Patients participating/participated in the PRIORITY-CHF study (may be alive or deceased at the time of inclusion to this study).
• Established diagnosis of HFpEF (presence of typical signs and symptoms of HF (see Appendix A) and LVEF ≥50%) at any time during participation in the PRIORITY-CHF study.

The following criteria apply for inclusion of patients into the prospective part of the study:

• Provided written informed consent for the prospective phase of the study.
• Presence of left ventricular wall thickness >12 mm.

• Presence of at least three of "red flags" or additional signs for having high-risk of ATTR-CM (evaluation based on medical history of HF and concomitant diseases, family history, results of previous ECG, Echo-CG/cardiac MRI, laboratory data):

  • >65 age (during participation in the PRIORITY-CHF study)
  • Conduction system disease (atrioventricular block, left bundle branch block, long QRS complex, sick sinus syndrome)/pacemaker
  • Atrial fibrillation
  • Pseudoinfarct pattern on the ECG (when hemodynamically significant stenosis is absent);
  • Disproportion of QRS voltage to the degree of increased LV wall thickness on imaging methods
  • Grade 2 or worse diastolic dysfunction
  • Decreased longitudinal strain with apical sparing
  • Diffuse subendocardial or transmural late gadolinium enhancement on cardiac MRI with increased extracellular volume fraction
  • Persistent low-level troponin elevation
  • Elevated NT-proBNP level
  • Right ventricular (RV) wall thickness more than 6 mm
  • Pericardial effusion in patients with LV-hypertrophy
  • Restrictive pattern in patients with LV-hypertrophy
  • Atrial enlargement with the normal ventricular volumes
  • Bilateral carpal tunnel syndrome
  • Lumbar/cervical spinal stenosis
  • Spontaneous biceps tendon rupture
  • Hip or knee replacement
  • Peripheral neuropathy
  • Family history of neuropathy
  • Intolerance/poor tolerance to vasodilating antihypertensive medications
  • Orthostatic hypotension
  • Gastroparesis
  • Urinary incontinence (neurogenic bladder), recurrent urinary infections,
  • Erectile dysfunction
  • Other autonomic dysfunction, such as gastrointestinal motility disorders (constipation, early satiety, chronic diarrhea, nausea/vomiting), syncope, anhidrosis)

Exclusion Criteria:

Exclusion criteria for the retrospective phase are:

• Any severe condition that, in opinion of the physician, will limit patient's life span to 12 months or less from the inclusion to this study.
• Current participation in any interventional trial (i.e. at the time of inclusion to this study).

The following criteria apply for exclusion of patients from the prospective part of the study:

• Patients with previously established (and documented) ATTR-CM.
• Patients with previous positive hematological test result on evaluating AL-amyloidosis in the anamnesis (monoclonal protein is identified by SIFE/UIF) and the serum FLC ratio (kappa/lambda) is in outside of the normal range).

If the hematological test on evaluating AL amyloidosis is negative, or there is no such test performed in the patient's medical history, the patient may be enrolled to this study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of ATTR-CM in patients with HFpEF in routine clinical practice in the Russian Federation	In order to achieve primary objective, the proportion of patients with confirmed diagnosis of ATTR-CM (at the end-of-study visit, according to the results of comprehensive cardiologic examination) among patients with HFpEF who were enrolled to retrospective phase and prospective phase of this study will be calculated.	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
demographic and clinical characteristics, and test results	In order to achieve the secondary objectives, the following demographic and clinical characteristics, and test results (with additional available data as needed) will be assessed in patients who were enrolled to the prospective phase of this study: Mean age (years) at the diagnosis of HFpEF during participation in the PRIORITY-CHF study; Mean age at the diagnosis of ATTR-CM confirmed in this study (assessed in patients with confirmed ATTR-CM); Mean and median time from the diagnosis of HFpEF to the confirmed diagnosis of ATTR-CM (assessed in patients with confirmed ATTR-CM); Distribution of patients by age group sex, race, ethnicity and geographic regions; Mean body mass index (BMI) and proportion of patients with different BMI dimensions; Proportion of patients with a history of unexplained weight loss (≥5 kg) at any point; Mean blood pressure (BP) and heart rate; Proportion of patients with presence of negative lifestyle factors (smoking and alcohol abuse); etc.	Up to 12 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Redacted CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2023
• Primary Completion (Actual): June 25, 2024
• Study Completion (Actual): June 25, 2024

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Transthyretin amyloidosis cardiomyopathy, heart failure with preserved ejection fraction, ATTR, CM, HFpEF
• Additional Relevant MeSH Terms: Nervous System Diseases; Cardiovascular Diseases; Heart Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Proteostasis Deficiencies; Amyloid Neuropathies; Amyloidosis, Familial; Heart Failure; Cardiomyopathies; Amyloidosis; Amyloid Neuropathies, Familial
• Other Study ID Numbers: D8450R00006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No